Clinical Trials /

Lutathera in People With Pancreatic Neuroendocrine Tumors That Have Spread to the Liver

NCT04544098

Description:

This study will look at whether it is practical and safe to give Lutathera directly into an artery of the liver (hepatic intraarterial infusion). The researchers will compare the effects of hepatic intraarterial infusion in the liver with the effects of the standard approach (intravenous infusion in the arm). The researchers will also determine whether Lutathera is effective against participants' cancer.

Related Conditions:
  • Pancreatic Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Lutathera in People With Pancreatic Neuroendocrine Tumors That Have Spread to the Liver
  • Official Title: A Pilot Study Investigating Intrahepatic Arterial And Intravenous Infusion Of The Radiolabeled Somatostatin Agonist 177Lu-DOTATATE In Patients With Liver-Dominant Metastatic Pancreatic Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: 20-232
  • NCT ID: NCT04544098

Conditions

  • Pancreatic Neuroendocrine Tumors
  • Liver-Dominant Metastatic Pancreatic Neuroendocrine Tumors

Interventions

DrugSynonymsArms
177Lu-DOTATATEPRRT with 177Lu-DOTATATE

Purpose

This study will look at whether it is practical and safe to give Lutathera directly into an artery of the liver (hepatic intraarterial infusion). The researchers will compare the effects of hepatic intraarterial infusion in the liver with the effects of the standard approach (intravenous infusion in the arm). The researchers will also determine whether Lutathera is effective against participants' cancer.

Trial Arms

NameTypeDescriptionInterventions
PRRT with 177Lu-DOTATATEExperimentalPatients will undergo a routine 68Ga-DOTATATE PET/CT. Patients with sufficient tumor uptake will be offered therapy with 177Lu-DOTATATE. The treatment regimen will consist of four administrations of 177Lu-DOTATATE-two intra-arterial followed by two intravenous, two months apart (+/- 2 weeks), with renal protective amino acid solution co-administration.
  • 177Lu-DOTATATE

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects affected by histologically proven, somatostatin-receptor positive,
             progressive, nonresectable, liver-dominant metastatic pancreatic neuroendocrine tumors
             (Pan-NETs), G1, G2 and G3, according to the new WHO classification of 2017.

               1. Ability to understand and willingness to sign a written informed consent document

               2. Aged 18 years or older

               3. Histologically proven or cytologically confirmed, non-resectable, pancreatic NETs
                  (PanNETs) with liver-dominant disease

               4. Measurable disease as defined by RECIST 1.1 with at least one dimension ≥ 1.0 cm

               5. PanNET of grade 1, 2 and 3 according to WHO 2017

               6. Progression of disease defined by one of the following occurring within 6 months
                  of study entry:

                    1. At least a 20% increase in radiologically or clinically measurable disease;

                    2. Appearance of any new lesion;

                    3. Symptomatic disease (including worsening hormonal symptoms or symptoms
                       related to tumor burden);

               7. Overexpression of somatostatin receptors of the target lesions at 68Ga-DOTATATE
                  PET/CT with SUV of lesions greater than normal liver at least in 1 metastasis.

               8. ECOG performance status 0 or 1 (Karnofsky ≥ 70%).

               9. Women of childbearing potential and men must agree to use adequate contraception
                  prior to study entry and for the duration of study participation.

              10. Previous local therapy (e.g., chemoembolization or bland embolization) is allowed
                  if completed >6 weeks prior to study entry. For such patients, there must be
                  either progression of measurable disease documented within the treatment field,
                  or measurable progressive disease outside the treatment field prior to study
                  entry.

              11. Previous oral chemotherapy, biotherapy (such as Interferons or Everolimus) and/or
                  investigational agents are allowed if completed >4 weeks prior to study entry For
                  patients who received systemic therapy prior to study entry, there must be
                  documented progression of measurable disease since receiving systemic therapy
                  prior to study entry.

              12. Patients must not be candidate for potentially curative surgery. Prior surgery is
                  allowed no less than 6 weeks prior to study entry. Note: Patients who have
                  disease that is amendable to resection but who are not a surgical candidate for
                  other medical reasons would be permitted.

        Exclusion Criteria:

          1. Women who are pregnant or breastfeeding

          2. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 177Lu-DOTATATE as assessed from medical records.

          3. Life expectancy < 6 months as assessed by the treating physician.

          4. Over 80% liver involvement by tumor per the judgement of the radiologist

          5. Poorly differentiated pancreatic neuroendocrine neoplasms (Pancreatic Neuroendocrine
             Carcinoma), small and large cell type; Mixed Neuroendocrine-Nonneuroendocrine Neoplasm
             (MiNEN).

          6. Presence of somatostatin receptor negative lesions.

          7. Prior treatment with other radiolabeled somatostatin analogs.

          8. Prior systemic chemotherapy, except oral chemotherapy with capecitabine + temozolomide

          9. Contraindication to angiography/embolization including:

               1. Patients cannot receive contrast

               2. Severe allergic reaction to contrast despite premedication. Patients in who IV
                  contrast is contraindicated are recommended to have MRI abdomen and noncontrast
                  chest CT scan.

               3. Poor renal function not on dialysis

               4. Other, based on judgment of the investigator

         10. Main portal vein tumor thrombus.

         11. Deteriorated renal function:

               1. Serum creatinine >1.7 mg/dL OR

               2. EGFR <30 ml/min

         12. Deteriorated bone marrow function:

               1. Hb <8.0 g/dL;

               2. WBC <3000/mm3;

               3. ANC<1500/mm3;

               4. Platelets <75.000/mm3

         13. Deteriorated liver function:

               1. INR > 2.0 for patients that are not on Coumadin or Xarelto

               2. PTT > 2x ULN

               3. Total bilirubin >3 mg/dl

               4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

         14. Clinically relevant toxicities from prior therapies that have not resolved to grade 1
             or grade 0

         15. Previous liver radioembolization with 90Y-microspheres.

         16. Known brain metastases and/or carcinomatous meningitis, unless these metastases have
             been treated and stabilized.

         17. Uncontrolled diabetes mellitus as defined by a HbA1c >9%

         18. Inability to interrupt short-acting Octreotide for 24 h before and 24 h after the
             administration of 177Lu-DOTATATE; inability to have an interval between Octreotide LAR
             and 177Lu-DOTATATE of ≥4 weeks

         19. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

         20. Prior external beam radiation therapy involving >25% of the bone marrow.

         21. Unmanageable urinary incontinence rendering the administration of 177Lu-DOTATATE
             unsafe

         22. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
             situ of the uterine cervix, unless definitively treated and with no evidence of
             recurrence.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients who successfully complete 2 IA injections
Time Frame:2 years
Safety Issue:
Description:Feasibility will be defined as at least 7 or more patients out of 10 patients who successfully complete 2 IA injections.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • 177Lu-DOTATATE
  • Pan-NETs
  • Intrahepatic Arterial
  • Intravenous Infusion
  • 20-232

Last Updated

September 3, 2020